Orgo Exam 3: pKa Values, Bases + Nucleophiles, IUPAC Names of Common Alkenes

-10

-9

-8

-8

-3.0

-1.7

-1.4

-1.2

19.2

25

35

38

41-43

44

50

3.2

4.7

5.3

9

9.3

10

10

15.7

16

18

NaH

Strong base
Weak nucleophile

t-BuOK (pronounced “t-butoxide” or potassium tert-butoxide

Strong base
Weak nucleophile

DBN

Strong base

Weak Nucleophile

DBU

Strong base
Weak nucleophile

OH-

Strong base
Strong nucleophile

OMe-

Strong base
Strong Nucleophile

OEt-

Strong base
Strong nucleophile

I-

Weak base
Strong nucleophile

Br-

Weak base
Strong nucleophile

Cl-

Weak base
Strong nucleophile

RS-

Weak base
Strong nucleophile

HS-

Weak base
Strong nucleophile

RSH

Weak base
Strong nucleophile

H2S

Weak base
Strong nucleophile

H2O

Weak base
Weak nucleophile

MeOH

Weak base
Weak nucleophile

NH3

Weak base
Weak nucleophile

EtOH

Weak base
Weak nucleophile

LDA

bulky, strong base that removes protons but doesn’t act as a nucleophile — perfect for controlled deprotonation and E2 reactions

Ethylene

Propylene

Styrene

Vinyl

Allyl

Phenyl

Methylene

Reaction of Alkenes (11 mechanisms)

1. Hydrohalogenation

2. Anti-Markonikov

3. Acid-Catalyzed hydration

4. Oxymercuration-Memercuration

5. Hydroboration-Oxidation

6. Catalytic Hydrogenation

7. Halogenation

8. Halohydrin Formation

9. Anti-Dihydroxylation

10. Syn-Dihydroxylation

11. Oxidative cleavage

1) Hydrohalogenation

• Alkene + HX (X = halide, such as Cl, Br, I)

• Halide is added onto MORE SUBSTITUTED carbon

• Markonikov additions

• Formation of carbocation

  • Racemization and rearrangement are possibilities

    • RING EXPANSION can also be a result (form of rearrangement)

Markonikov’s rule

In the addition of HX or H2O to an alkene, H adds to the less substituted C

2) Anti-Markonikov

• Only occurs with ROOR (peroxide), HBr, and hv (radical)

• HCl and HI do not undergo rxn because racial reactions of HCl and HI are not spontaneous

3) Acid-Catalyzed Hydration

• OH group added to MORE substituted carbon in alkene

• When the carbon is MORE substituted, reaction rate INCREASES

• Catalysts

1) cat. H₂SO₄

2) H2O

The addition and elimination of water are in equilibrium

• Carbocation forms in reaction mechanism, so rearrangement is possible!!!!!

Equilibrium in acid-catalyzed hydration reaction

4) Oxymercuration-Demercuration

• Alternative hydration to alkene (different from acid-catalyzed hydration because there is NO formation of carbocation intermediate, so there will never be rearrangement)

• Regiospecific: OH will ONLY be added to the more substituted C in the alkene

• If addition of OH creates chiral center —> enantiomers will form

1) Hg(OAc)₂, HO-H

2) NaBH₄

4B) Alkoxymercuration-Demercuration

• Instead of water as reagant, alcohols and amines can be used

• Basically same thing as oxymercuration-demercuration

5) Hydroboration-Oxidation

1) BH₃, THF

2) H₂O₂

Result: Anti-Markonikov addition of OH (because anti-Markonikov allows less steric hindrance)

• Boron has similar structure to carbocation —> forms dime

• NO REARRANGEMENT in Hydroboration-Oxidation reaction

• Stereospecificity: Syn-addition of H and OH

6) Catalytic Hydrogenation

• Syn addition because two flat surfaces interacting

• Less steric hindrance with syn addition

• Possible metal catalysts: Pt, Pd, Ni

7) Halogenation

• Result: anti-addition of 2 halogens across alkene

1) X₂

2) CCl₄ or CHCl₃ ← NON-nucleophilic solvent

Can form cis or trans isomer depending on the configuration of starting alkene

8) Halohydrin Formation

• When bromination reaction performed in NUCLEOPHILIC solvent such as H₂O or ROH, the bromination is “captured”  by the solvent

• Result: anti-addition of X and OH/OR

9) Anti Dihydroxylation

Result: anti-addition of 2 OH groups —> forms trans diols

• Epoxide controls the stereochemistry

• mCPBA is popular reagant

Common peroxides

• Acetic acid

• Peroxyacetic acid

• Benzoic acid

• Meta-chloroperoxy benzoic acid (mCPBA)

Acetic acid

Peroxyacetic acid

Benzoic acid

meta-chloroperoxybenzoic acid (mCPBA)

Commonality between anti-addition reactions:

Reactions go through 3-membered ring intermediate

10) Syn Dihydroxylation

Reagants:

Either:

• 1) KMnO₄, NaOH, cold

• 2) OsO₄, NMO

All syn-addition reactions and what they add:

All anti-addition reactions and what they add:

All mixed addition reactions and what they add

11) Oxidative Cleavage: 2 possible reactions

• 11.1 Ozonolysis

• 11.2 By KMnO₄, warm condition: an aldehyde is further oxidized to a carboxylic acid

11.1) Ozonolysis

11.2) Oxidative Cleavage By KMnO4

How to deprotonate terminal alkyne

Equilibrium favors WEAK ACID so conjugate acid of the reactant base must be weaker than reactant acid (alkyne). Basically, the base is only strong enough if its conjugate acid has a pKa HIGHER THAN 25.

Isobutyl alcohol

Ethylene glycol

1) excess NaNH₂

2) H₂O

Elimination

• Vicinal or geminal dibromide converted to alkyne

HX

Hydrohalogenation

• Alkyne + HX —> Markonikov addition (excess HX gives TWO addition rxns, forming geminal dihalide)

H₂SO₄, H₂O, HgSO₄

Acid Catalyzed Hydration

• Terminal alkyne + ____ —> Markonikov addition of H and OH to create enol —> quickly tautomerizes to ketone

1) R₂BH (9-BBN)

2) H₂O₂, NaOH

Hydroboration-Oxidation

• Terminal alkyne + ___ —> anti-Markonikov addiiton of H and OH —> enol —> tautomerizes to aldehyde

X_{2 ⁺} non-nucleophilic solvent

Halogenation

• Alkyne + _____ —> addition of two halogens across the double bond

1) O₃

2) H₂O

Ozonolysis (alkyne)

• Oxidative cleavage of C-C triple bond 

• Internal alkyne converted into two carboxylic acid

• Terminal alkynes converted into carboxylic acid and carbon dioxide

H₂, Lindlars Catalyst (Pd/BaSO₄, quinoline)

Hydrogenation

• When treated with these reactants, alkyne → cis alkene

H₂, Pt

Hydrogenation

• Alkyne → alkane

Na(s), NH₃ (l)

Dissolving metal reduction

• When treated with these reagents, internal alkyne converted to trans alkyne

Br₂, hv

Radical bromination

• Alkane (CC single bond) undergoes bromination with installation of Br at most substituted position

Cl₂, hv

Radical chlorination

• Alkane (CC single bond) undergoes Chlorination

• Less selective than bromination but faster → most useful in situations where monochlorination results in ONLY ONE regiochemical outcome

HBr, ROOR (peroxide)

Hydrobromination

• Alkene undergoes anti-Markonikov addition of H and Br

NBS, hv

Allylic bromination

• Install bromine atom at allylic position of alkene

• Consider rearrangement!

NaH

Very strong base used to deprotonate alcohols —> alkoxide ion

Na

Will react w/ alcohol to liberate hydrogen gas → Alkoxide ion

NaBH₄, MeOH

• Reduces once

Reducing agent (source of nucleophilic hydride) → can be used to reduce ketones or aldehydes to alcohols

1) LiAlH₄

2) H₃O^₊

Strong reducing agent (source of nucleophilic hydride)

• Can be used to reduce ketones, aldehydes, or carboxylic acids

H₂, Pt

Reduces alkenes and alkynes to alkanes

Mg

Make Grignard Reagant

TMSCl, Et₃N

Protecting group